Nueva mutación para xantomatosis cerebrotendinosa causa demencia familiar temprana en Colombia

Introduction: Cerebrotendinous xanthomatosis is an infrequent cause of dementia. It is an autosomal recessive disorder with clinical and molecular heterogeneity.Objective: To identify the presence of a possible mutation in a Colombian family with several affected siblings and clinical characteristics compatible with cerebrotendinous xanthomatosis associated to early dementia.Materials and methods: We studied a series of cases with longitudinal follow-up and genetic analysis.Results: These individuals had xanthomas, mental retardation, psychiatric disorders, behavioral changes, and multiple domains cognitive impairment with dysexecutive dominance that progressed to early dementia. CYP27A1 gene coding region sequencing revealed a novel mutation (c.1183_1184insT).Conclusion: The mutation found in this family is responsible for the described dementia features. Early identification of familial history with mental retardation, xanthomas and cognitive impairment might prevent the progression to this treatable type of dementia. Even though this mutation lies in the most frequently mutated codon of CYP27A1 gene, it has not been reported previously.Introducción. La xantomatosis cerebrotendinosa es una causa poco frecuente de demencia. Es un trastorno autosómico recesivo con heterogeneidad clínica y molecular.Objetivo. Identificar la presencia de una posible mutación en una familia colombiana con varios hermanos afectados y con características clínicas indicativas de xantomatosis cerebrotendinosa asociada a demencia precoz.Materiales y métodos. Se estudió una serie de casos, con seguimiento longitudinal y análisis genético.Resultados. Estos individuos tenían xantomas, retraso mental, trastornos psiquiátricos, cambios de comportamiento y alteraciones cognitivas de múltiples dominios con predominio de la disfunción ejecutiva, que progresaron a demencia temprana. Se identificó una nueva mutación (c.1183_1184insT) en el gen CYP27A1.Conclusión. La mutación encontrada en esta familia es responsable de la demencia descrita en los sujetos de estudio. La detección temprana de una historia familiar con retraso mental, xantomas y deterioro cognitivo, podría prevenir la progresión de este tipo de demencia tratable. A pesar de que esta mutación se encuentra en el codón más frecuentemente mutado del gen CYP27A1, no se había informado anteriormente

Evaluación polisomnográfica de bebés no infectados nacidos de madres VIH-1 positivas

SUMMARY: Introduction: Type 1 human immunodeficiency virus (HIV-1) is a lymphotropic and neurotropic retrovirus. Thus, it causes immunological and neurological alterations particularly in children. In the neonatal period the maturational changes of the central nervous system occur rapidly, and their alteration can be reflected in processes such as the sleep-awake pattern. Objective: To evaluate sleep organization, EEG and respiratory pattern in newborns to HIV-1 positive mothers. Methods: 22 infants underwent polysomnography. Delta brushes number in REM and NREM sleep, duration of interburst interval and interhemispheric synchrony were used to calculate EEG maturation. Analysis of the sleep architecture was based on polysomnographic sleep percentage of REM, NREM and transitional sleep to total sleep time. Results: The difference between electroencephalographically calculated and clinically calculated conceptional age was less than two weeks. Percentages of REM and NREM sleep ranged from 39-64 and 30-58 with a median of 52.5 and 36.5 respectively. Concordance was lower in newborns who had high transitional sleep percentages, compared to that in newborns who did not have high such characteristic (p<0.05). Discussion: Despite intrauterine exposure to HIV-1 and to antiretroviral drugs we did not observe a significant effect on EEG maturation. The decreased concordance in newborns with high transitional sleep percentages would suggest an alteration in the maturation process, but this aspect itself is not sufficient to consider that intrauterine exposure to HIV-1 and antiretrovirals affect the entire sleep architecture. Future studies should clarify whether the decreased concordance between behavior and NREM sleep is replicableRESUMEN: Introducción: el virus de la inmunodeficiencia humana tipo 1 (VIH-1) es un retrovirus linfotrópico y neurotrópico. Esta característica genera alteraciones inmunológicas y neurológicas particularmente en niños. Durante el período neonatal la maduración del sistema nervioso central ocurre rápidamente, y su alteración puede perturbar diferentes aspectos del desarrollo tales como el ciclo sueño-vigilia. Objetivo: evaluar la organización del sueño y el patrón electroencefalográfico y respiratorio en recién nacidos VIH-1 negativos hijos de madres VIH-1 positivas. Métodos: se les hizo polisomnografía a 22 infantes. Se calculó la maduración electroencefalográfica usando el número de ondas delta en sueño REM y NREM, la duración del intervalo interespigas y la sincronía interhemisferica. Se analizó la arquitectura del sueño con base en el porcentaje de sueño REM, NREM y sueño transicional con relación al tiempo total de sueño. Resultados: la diferencia entre la edad electroencefalográfica y la edad concepcional calculada fue menor de dos semanas. El rango del porcentaje de sueño REM y NREM fue 39-64 y 30-58 y la media fue de 52,5 y 36,5, respectivamente. La concordancia en los recién nacidos con alto porcentaje de sueño transicional fue menor comparada con la de los neonatos con menor porcentaje de sueño transicional (p<0,05). Discusión: a pesar de la exposición intrauterina al VIH1 y a los antirretrovirales, no se evidenciaron cambios significativos en la maduración electroencefalográfica. La disminución de la concordancia en neonatos con alto porcentaje de sueño transicional podría sugerir una alteración en el proceso de maduración, pero este aspecto en particular no es suficiente para considerar que la exposición intrauterina al VIH-1 y a los antirretrovirales afecta toda la arquitectura del sueño. Estudios posteriores deberían aclarar si la disminución entre la concordancia, el comportamiento y el porcentaje de sueño NREM es duplicabl

Frontotemporal Dementias in Latin America: History, Epidemiology, Genetics, and Clinical Research

Introduction: The historical development, frequency, and impact of frontotemporal dementia (FTD) are less clear in Latin America than in high-income countries. Although there is a growing number of dementia studies in Latin America, little is known collectively about FTD prevalence studies by country, clinical heterogeneity, risk factors, and genetics in Latin American countries. Methods: A systematic review was completed, aimed at identifying the frequency, clinical heterogeneity, and genetics studies of FTD in Latin American populations. The search strategies used a combination of standardized terms for FTD and related disorders. In addition, at least one author per Latin American country summarized the available literature. Collaborative or regional studies were reviewed during consensus meetings. Results: The first FTD reports published in Latin America were mostly case reports. The last two decades marked a substantial increase in the number of FTD research in Latin American countries. Brazil (165), Argentina (84), Colombia (26), and Chile (23) are the countries with the larger numbers of FTD published studies. Most of the research has focused on clinical and neuropsychological features (n = 247), including the local adaptation of neuropsychological and behavioral assessment batteries. However, there are little to no large studies on prevalence (n = 4), biomarkers (n = 9), or neuropathology (n = 3) of FTD. Conclusions: Future FTD studies will be required in Latin America, albeit with a greater emphasis on clinical diagnosis, genetics, biomarkers, and neuropathological studies. Regional and country-level efforts should seek better estimations of the prevalence, incidence, and economic impact of FTD syndromes

Effect of apolipoprotein genotype and educational attainment on cognitive function in autosomal dominant Alzheimers disease.

Autosomal dominant Alzheimers disease (ADAD) is genetically determined, but variability in age of symptom onset suggests additional factors may influence cognitive trajectories. Although apolipoprotein E (APOE) genotype and educational attainment both influence dementia onset in sporadic AD, evidence for these effects in ADAD is limited. To investigate the effects of APOE and educational attainment on age-related cognitive trajectories in ADAD, we analyzed data from 675 Presenilin-1 E280A mutation carriers and 594 non-carriers. Here we show that age-related cognitive decline is accelerated in ADAD mutation carriers who also have an APOE e4 allele compared to those who do not and delayed in mutation carriers who also have an APOE e2 allele compared to those who do not. Educational attainment is protective and moderates the effect of APOE on cognition. Despite ADAD mutation carriers being genetically determined to develop dementia, age-related cognitive decline may be influenced by other genetic and environmental factors

Sex differences in blood biomarkers and cognitive performance in individuals with autosomal dominant Alzheimer's disease

INTRODUCTION: Plasma tau phosphorylated at threonine 217 (P-tau217) and neurofilament light (NfL) have emerged as markers of Alzheimer's disease (AD) pathology. Few studies have examined the role of sex in plasma biomarkers in sporadic AD, yielding mixed findings, and none in autosomal dominant AD. METHODS: We examined the effects of sex and age on plasma P-tau217 and NfL, and their association with cognitive performance in a cross-sectional study of 621 Presenilin-1 E280A mutation carriers (PSEN1) and non-carriers. RESULTS: As plasma P-tau217 levels increase, cognitively unimpaired female carriers showed better cognitive performance than cognitively unimpaired male carriers. Yet, as disease progresses, female carriers had a greater plasma NfL increase than male carriers. There were no sex differences in the association between age and plasma biomarkers among non-carriers. DISCUSSION: Our findings suggest that, among PSEN1 mutation carriers, females had a greater rate of neurodegeneration than males, yet it did not predict cognitive performance. HIGHLIGHTS: We examined sex differences in plasma P-tau217 and NfL in Presenilin-1 E280A (PSEN1) mutation carriers and non-carriers. Female carriers had a greater plasma NfL increase, but not P-tau217, than male carriers. As plasma P-tau217 levels increase, cognitively unimpaired female carriers showed better cognitive performance than cognitively unimpaired male carriers. The interaction effect of sex by plasma NfL levels did not predict cognition among carriers

Sex differences in blood biomarkers and cognitive performance in individuals with autosomal dominant Alzheimer's disease

INTRODUCTION: Plasma tau phosphorylated at threonine 217 (P-tau217) and neurofilament light (NfL) have emerged as markers of Alzheimer's disease (AD) pathology. Few studies have examined the role of sex in plasma biomarkers in sporadic AD, yielding mixed findings, and none in autosomal dominant AD. METHODS: We examined the effects of sex and age on plasma P-tau217 and NfL, and their association with cognitive performance in a cross-sectional study of 621 Presenilin-1 E280A mutation carriers (PSEN1) and non-carriers. RESULTS: As plasma P-tau217 levels increase, cognitively unimpaired female carriers showed better cognitive performance than cognitively unimpaired male carriers. Yet, as disease progresses, female carriers had a greater plasma NfL increase than male carriers. There were no sex differences in the association between age and plasma biomarkers among non-carriers. DISCUSSION: Our findings suggest that, among PSEN1 mutation carriers, females had a greater rate of neurodegeneration than males, yet it did not predict cognitive performance. HIGHLIGHTS: We examined sex differences in plasma P-tau217 and NfL in Presenilin-1 E280A (PSEN1) mutation carriers and non-carriers. Female carriers had a greater plasma NfL increase, but not P-tau217, than male carriers. As plasma P-tau217 levels increase, cognitively unimpaired female carriers showed better cognitive performance than cognitively unimpaired male carriers. The interaction effect of sex by plasma NfL levels did not predict cognition among carriers

Effect of apolipoprotein genotype and educational attainment on cognitive function in autosomal dominant Alzheimer’s disease

Abstract Autosomal dominant Alzheimer’s disease (ADAD) is genetically determined, but variability in age of symptom onset suggests additional factors may influence cognitive trajectories. Although apolipoprotein E (APOE) genotype and educational attainment both influence dementia onset in sporadic AD, evidence for these effects in ADAD is limited. To investigate the effects of APOE and educational attainment on age-related cognitive trajectories in ADAD, we analyzed data from 675 Presenilin-1 E280A mutation carriers and 594 non-carriers. Here we show that age-related cognitive decline is accelerated in ADAD mutation carriers who also have an APOE e4 allele compared to those who do not and delayed in mutation carriers who also have an APOE e2 allele compared to those who do not. Educational attainment is protective and moderates the effect of APOE on cognition. Despite ADAD mutation carriers being genetically determined to develop dementia, age-related cognitive decline may be influenced by other genetic and environmental factors